Mechanisms mediating the ability of caffeine to influence MDMA (‘Ecstasy’)‐induced hyperthermia in rats

Abstract

Background and purpose: Caffeine exacerbates the hyperthermia associated with an acute exposure to 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') in rats. The present study investigated the mechanisms mediating this interaction. Experimental approach: Adult male Sprague-Dawley rats were treated with caffeine (10 mg·kg ) exacerbated MDMA-induced hyperthermia. Conclusions and implications:A mechanism comprising 5-HT and catecholamines is proposed to mediate MDMA-induced hyperthermia. A combination of adenosine A2A receptor antagonism and PDE inhibition can account for the exacerbation of MDMA-induced hyperthermia by caffeine.

Caffeine promotes dopamine D1 receptor-mediated body temperature, heart rate and behavioural responses to MDMA (‘ecstasy’)

“…Chaperon et al (2003) reported that dopamine D 1 and D 2 receptor may be involved in a co-operative manner to regulate core body temperature in rats where both SCH 23390 and the selective dopamine D 2 receptor antagonist L-741,626 were found to reverse hypothermia induced by the dopamine D 2 and D 3 receptor agonists trihydroxy-N-n-propylnoraporphine (TNPA) or PD 128907. Overall, the results are consistent with previous results from our laboratory in support of a dopamine-related mechanism that may account for a caffeine-induced switch from MDMA-induced hypo-to hyperthermia (Vanattou-Saïfoudine et al 2010).…”

“…Doses of caffeine and MDMA were chosen from previous reports of the interaction between caffeine and MDMA in rats (McNamara et al 2006(McNamara et al , 2007. The selective dopamine D 1/5 antagonist, SCH 23390, was used in this study at a dose of 1 mg/kg which blocks MDMA-induced hyperthermia and its exacerbation by caffeine in group-housed rats (Vanattou-Saïfoudine et al 2010). The selective dopamine D 2 receptor antagonist sulpiride was used in this study at a dose of 100 mg/kg.…”

“…The pharmacological effects of MDMA (Green et al 2003) and caffeine (Armstrong et al 2007;Cornelis and El-Sohemy 2007;Nawrot et al 2003) on behaviour, cardiovascular and body temperature regulation are individually reviewed elsewhere. Recently, we and others have reported that co-administration of caffeine exacerbates the acute toxicity of MDMA in rats, which is characterised by hyperthermia, tachycardia and lethality at higher doses (Vanattou-Saïfoudine et al 2010;McNamara et al 2006McNamara et al , 2007Camarasa et al 2006). This is a serious drug interaction, the mechanism of which warrants further investigation.…”

IUGR with infantile overnutrition programs an insulin-resistant phenotype through DNA methylation of peroxisome proliferator–activated receptor-γ coactivator-1α in rats

“…The core body temperature was assessed rectally by a digital probe thermometer (Omron, Kyoto, Japan) following the method previously described (40). The spontaneous physical activity was recorded for 1 h in locomotion cages (45 cm × 45 cm) by using AniLab Software (AniLab Software & instruments, Ningbo, China) following the manufacturer's instructions.…”

Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats

“…Adenosine A 1 receptors have a widespread distribution in the brain, with highest levels in the hippocampus, cerebral cortex, hypothalamus and cerebellum, and low levels in the basal ganglia, while A 2A receptors are found mainly in dopamine rich brain regions such as the striatum and nucleus accumbens. It is the effect of caffeine on dopamine release that is commonly attributed to the toxic effects (hyperthermia, cardiovascular toxicity and seizure threshold) of its coadministration with MDMA (Vanattou-Saifoudine et al, 2010b;Vanattou-Saifoudine et al, 2010a).…”